2023
A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better
Djureinovic D, Weiss S, Krykbaeva I, Qu R, Vathiotis I, Moutafi M, Zhang L, Perdigoto A, Wei W, Anderson G, Damsky W, Hurwitz M, Johnson B, Schoenfeld D, Mahajan A, Hsu F, Miller-Jensen K, Kluger Y, Sznol M, Kaech S, Bosenberg M, Jilaveanu L, Kluger H. A bedside to bench study of anti-PD-1, anti-CD40, and anti-CSF1R indicates that more is not necessarily better. Molecular Cancer 2023, 22: 182. PMID: 37964379, PMCID: PMC10644655, DOI: 10.1186/s12943-023-01884-x.Peer-Reviewed Original ResearchConceptsStable diseasePartial responseMacrophage populationsThree-drug regimenUnconfirmed partial responsePhase I trialLimited treatment optionsMonocyte/macrophage populationNon-classical monocytesMurine melanoma modelTreatment-related changesResultsThirteen patientsWorse survivalI trialInflammatory tumorPatient populationTreatment optionsImmune cellsDisease progressionMurine studiesPreclinical modelsResistant melanomaAntigen presentationMurine modelCyTOF analysis
2021
A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1
Weiss SA, Djureinovic D, Jessel S, Krykbaeva I, Zhang L, Jilaveanu L, Ralabate A, Johnson B, Levit NS, Anderson G, Zelterman D, Wei W, Mahajan A, Trifan O, Bosenberg M, Kaech SM, Perry CJ, Damsky W, Gettinger S, Sznol M, Hurwitz M, Kluger HM. A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non–Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1. Clinical Cancer Research 2021, 27: 4757-4767. PMID: 34140403, PMCID: PMC9236708, DOI: 10.1158/1078-0432.ccr-21-0903.Peer-Reviewed Original ResearchConceptsAnti-PD-1/PD-L1Non-small cell lung cancerCell lung cancerRenal cell carcinomaPD-L1Lung cancerDisease progressionCommon treatment-related adverse eventsPD-1/PD-L1 inhibitorsTreatment-related adverse eventsPhase 2 doseSubstantial clinical challengeUnconfirmed partial responseDose-limiting toxicityPD-L1 inhibitorsPhase I trialDose-escalation designPro-inflammatory cytokinesMultiple tumor typesAsymptomatic elevationStable diseaseIntolerable toxicityAdverse eventsMedian durationPartial response
2019
Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab
Hamid O, Molinero L, Bolen CR, Sosman JA, Muñoz-Couselo E, Kluger HM, McDermott DF, Powderly J, Sarkar I, Ballinger M, Fassò M, O'Hear C, Chen DS, Hegde PS, Hodi FS. Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. Clinical Cancer Research 2019, 25: 6061-6072. PMID: 31358540, DOI: 10.1158/1078-0432.ccr-18-3488.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorFatigueFemaleFeverFollow-Up StudiesHumansMaleMelanomaMiddle AgedPrognosisProgression-Free SurvivalPruritusRetrospective StudiesSeverity of Illness IndexSkinSkin NeoplasmsT-Lymphocytes, CytotoxicTranscriptomeYoung AdultConceptsTreatment-related adverse eventsAdverse eventsOverall survivalMetastatic melanomaCommon treatment-related adverse eventsMost treatment-related adverse eventsAntitumor T-cell activityMeaningful long-term survivalActivity of atezolizumabEfficacy-evaluable patientsPhase Ia studyTreatment-related deathsMedian overall survivalPD-L1 expressionProgression-free survivalCohort of patientsPhase I trialT cell activityOverall response rateBiological correlatesLong-term safetyLong-term survivalPrimary study objectiveDurable responsesGrade 1/2
2014
Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL).
Sznol M, Kluger H, Callahan M, Postow M, Gordon R, Segal N, Rizvi N, Lesokhin A, Atkins M, Kirkwood J, Burke M, Ralabate A, Rivera A, Kronenberg S, Agunwamba B, Feely W, Hong Q, Krishnan S, Gupta A, Wolchok J. Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). Journal Of Clinical Oncology 2014, 32: lba9003-lba9003. DOI: 10.1200/jco.2014.32.18_suppl.lba9003.Peer-Reviewed Original ResearchClinical activityTreatment-related adverse eventsMT statusManageable safety profilePrior systemic therapyPhase I trialMajority of ptsBRAF mutation statusBRAF MTIPI therapyStage M1cPrior therapyMedian durationObjective responseSystemic therapyAdvanced melanomaAdverse eventsConcurrent therapyI trialOS ratesSafety profileTumor reductionTumor responseGrade 3Wk 24Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial.
Hodi F, Sznol M, Kluger H, McDermott D, Carvajal R, Lawrence D, Topalian S, Atkins M, Powderly J, Sharfman W, Puzanov I, Smith D, Leming P, Lipson E, Taube J, Anders R, Horak C, Kollia G, Gupta A, Sosman J. Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial. Journal Of Clinical Oncology 2014, 32: 9002-9002. DOI: 10.1200/jco.2014.32.15_suppl.9002.Peer-Reviewed Original Research
2013
Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538).
Sznol M, Kluger H, Hodi F, McDermott D, Carvajal R, Lawrence D, Topalian S, Atkins M, Powderly J, Sharfman W, Puzanov I, Smith D, Wigginton J, Kollia G, Gupta A, Sosman J. Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538). Journal Of Clinical Oncology 2013, 31: cra9006-cra9006. DOI: 10.1200/jco.2013.31.18_suppl.cra9006.Peer-Reviewed Original ResearchPhase I trialI trialInhibitory immune checkpoint receptorsDrug-related AEsDrug-related diarrheaDrug-related pneumonitisAcceptable safety profilePhase III trialsOverall survival dataImmune checkpoint receptorsCycles of treatmentLong-term safetyMonoclonal antibody nivolumabActivated T cellsGr 3Cohort expansionECOG PSMedian OSPrior therapyIII trialsAdvanced melanomaAntibody nivolumabDose escalationPD-1Checkpoint receptorsSurvival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538).
Sznol M, Kluger H, Hodi F, McDermott D, Carvajal R, Lawrence D, Topalian S, Atkins M, Powderly J, Sharfman W, Puzanov I, Smith D, Wigginton J, Kollia G, Gupta A, Sosman J. Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538). Journal Of Clinical Oncology 2013, 31: cra9006-cra9006. DOI: 10.1200/jco.2013.31.15_suppl.cra9006.Peer-Reviewed Original ResearchSafety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL).
Wolchok J, Kluger H, Callahan M, Postow M, Gordon R, Segal N, Rizvi N, Lesokhin A, Reed K, Burke M, Caldwell A, Kronenberg S, Agunwamba B, Feely W, Hong Q, Horak C, Korman A, Wigginton J, Gupta A, Sznol M. Safety and clinical activity of nivolumab (anti-PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL). Journal Of Clinical Oncology 2013, 31: 9012-9012. DOI: 10.1200/jco.2013.31.15_suppl.9012.Peer-Reviewed Original ResearchObjective response rateRelated adverse eventsPhase III trialsConcurrent therapyIII trialsPD-1Clinical activityCTLA-4/PDIpilimumab combination therapyCTLA-4 blockadeManageable safety profilePhase 1 studyPhase I trialImmune checkpoint receptorsIpilimumab therapyMonotherapy dataPrior therapySymptom resolutionAdverse eventsI trialAdvanced melanomaDurable CRCheckpoint receptorsSafety profileCombination therapySurvival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up.
Drake C, McDermott D, Sznol M, Choueiri T, Kluger H, Powderly J, Smith D, Sankar V, Gutierrez A, Wigginton J, Kollia G, Gupta A, Atkins M. Survival, safety, and response duration results of nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in a phase I trial in patients with previously treated metastatic renal cell carcinoma (mRCC): Long-term patient follow-up. Journal Of Clinical Oncology 2013, 31: 4514-4514. DOI: 10.1200/jco.2013.31.15_suppl.4514.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaOverall survivalDrug-related AEsGrade 3 pneumonitisMedian overall survivalAcceptable safety profilePhase III trialsPD-1 ligandsPhase I trialLong-term patientsPD-1 receptorImmune checkpoint receptorsRenal cell carcinomaLong-term safetyT cell activationPopulation of ptsPrior therapyTreatment discontinuationAdverse eventsIII trialsMedian durationUnacceptable toxicityComplete responseDeath-1I trial